lncNBAT1/APOBEC3A is a mediator of HBX-induced chemoresistance in diffuse large B cell lymphoma cells.
lncNBAT1/APOBEC3A is a mediator of HBX-induced chemoresistance in diffuse large B cell lymphoma cells.
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DOI：
10.1016/j.omtn.2022.01.015
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发表时间：
2022-03-08
期刊：
影响因子：
--
通讯作者：
Kang J
中科院分区：
文献类型：
--
作者：
Li J;Chen Y;Guo X;Bai X;Xu X;Han T;Tan A;Liu N;Xia Y;Sun Q;Guo X;Chen J;Kang J
感染B型肝炎病毒（HBV）的弥漫性大B细胞淋巴瘤（DLBCL）患者化疗疗效较差，预后较差。目前尚不清楚长链非编码RNA（lncRNA）是否可作为DLBCL和HBV感染患者化疗耐药性的预后和治疗靶点。在这里，我们发现HBV的核心成分（HBX）直接上调lncNBAT 1的表达，这与HBV感染DLBCL患者的化疗结果密切相关。IncNBAT 1的上调降低了DLBCL细胞对诱导S期阻滞的化疗药物（甲氨蝶呤[MTX]或阿糖胞苷[Ara-C]）的敏感性，而IncNBAT 1的敲低显著减轻了表达HBX的DLBCL的化疗耐药性。在机制上，lncNBAT 1可与信号转导和转录激活因子1（STAT 1）相互作用，阻止其在功能性靶基因载脂蛋白B mRNA编辑酶催化亚基3A（APOBEC 3A）启动子区富集，抑制APOBEC 3A表达，诱导DLBCL细胞对MTX耐药。此外，临床数据分析显示，lncNBAT 1和APOBEC 3A表达与DLBCL患者的不良预后和短生存期密切相关。我们的研究结果表明，一个潜在的预后标志物和候选lncRNA治疗乙肝病毒感染的DLBCL个体的目标。Li等人确定lncNBAT 1是DLBCL中HBX诱导的化学抗性的关键介质。lncNBAT 1与STAT 1相互作用并阻止其在APOBEC 3A启动子区结合，抑制APOBEC 3A转录。这些发现表明lncNBAT 1作为一个潜在的预后标志物和候选lncRNA治疗HBV感染的DLBCL个体的目标。
Individuals with diffuse large B cell lymphoma (DLBCL) infected with hepatitis B virus (HBV) have worse chemotherapy efficacy and poorer outcomes. It is still unclear whether long noncoding RNAs (lncRNAs) serve as prognostic and therapeutic targets in the chemotherapy resistance of individuals with DLBCL and HBV infection. Here we found that the core component of HBV (HBX) directly upregulated the expression of lncNBAT1, which was closely associated with the chemotherapy outcomes of HBV-infected individuals with DLBCL. Upregulation of lncNBAT1 reduced the sensitivity of DLBCL cells to chemotherapeutic agents (methotrexate [MTX] or cytarabine [Ara-C]) that induced S phase arrest, whereas knockdown of lncNBAT1 significantly relieved the chemoresistance of HBX-expressing DLBCLs. Mechanistically, lncNBAT1 could interact with the signal transducer and activator of transcription 1 (STAT1) to prevent its enrichment at the promoter region of the functional target gene apolipoprotein B mRNA editing enzyme catalytic subunit 3A (APOBEC3A), inhibiting expression of APOBEC3A and inducing resistance to MTX in DLBCL cells. Furthermore, clinical data analysis showed that lncNBAT1 and APOBEC3A expression was closely related to the poor prognosis and short survival of individuals with DLBCL. Our findings suggest a potential prognostic marker and a candidate lncRNA target for treating HBV-infected individuals with DLBCL. Li et al. identified lncNBAT1 as a crucial mediator of HBX-induced chemoresistance in DLBCL. lncNBAT1 interacted with STAT1 and prevented its binding at the APOBEC3A promoter region, inhibiting APOBEC3A transcription. These findings suggested lncNBAT1 as a potential prognostic marker and a candidate lncRNA target for treating HBV-infected individuals with DLBCL.
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影响因子：
29.4
作者：
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通讯作者：
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影响因子：
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DOI：
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发表时间：
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期刊：
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